NDLI: A global sensitivity tool for cardiac cell modeling: Application to ionic current balance and hypertrophic signaling

Content Provider	IEEE Xplore Digital Library
Author	Sher, A.A. Cooling, M.T. Bethwaite, B. Tan, J. Peachey, T. Enticott, C. Garic, S. Gavaghan, D.J. Noble, D. Abramson, D. Crampin, E.J.
Copyright Year	2010
Description	Author affiliation: 4Faculty of Information Technology, Monash University, AUS, Australia (Bethwaite, B.; Tan, J.; Peachey, T.; Enticott, C.; Garic, S.; Abramson, D.) \|\| Department of Physiology, Anatomy and Genetics, University of Oxford, UK (Sher, A.A.; Noble, D.) \|\| Oxford University Computing Laboratory, University of Oxford, UK (Gavaghan, D.J.) \|\| Auckland Bioengineering Institute, University of Auckland, NZ, New Zealand (Cooling, M.T.; Crampin, E.J.)
Abstract	Cardiovascular diseases are the major cause of death in the developed countries. Identifying key cellular processes involved in generation of the electrical signal and in regulation of signal transduction pathways is essential for unraveling the underlying mechanisms of heart rhythm behavior. Computational cardiac models provide important insights into cardiovascular function and disease. Sensitivity analysis presents a key tool for exploring the large parameter space of such models, in order to determine the key factors determining and controlling the underlying physiological processes. We developed a new global sensitivity analysis tool which implements the Morris method, a global sensitivity screening algorithm, onto a Nimrod platform, which is a distributed resources software toolkit. The newly developed tool has been validated using the model of IP3-calcineurin signal transduction pathway model which has 30 parameters. The key driving factors of the IP3 transient behaviour have been calculated and confirmed to agree with previously published data. We next demonstrated the use of this method as an assessment tool for characterizing the structure of cardiac ionic models. In three latest human ventricular myocyte models, we examined the contribution of transmembrane currents to the shape of the electrical signal (i.e. on the action potential duration). The resulting profiles of the ionic current balance demonstrated the highly nonlinear nature of cardiac ionic models and identified key players in different models. Such profiling suggests new avenues for development of methodologies to predict drug action effects in cardiac cells.
Starting Page	1498
Ending Page	1502
File Size	1950974
Page Count	5
File Format	PDF
ISBN	9781424441235
ISSN	1557170X
DOI	10.1109/IEMBS.2010.5626841
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2010-08-31
Publisher Place	Argentina
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Computational modeling Analytical models Humans Sensitivity analysis Transient analysis Heart Cooling
Content Type	Text
Resource Type	Article
Subject	Signal Processing Biomedical Engineering Health Informatics Computer Vision and Pattern Recognition

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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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